Neuropsychological intermediate phenotypes as tools for genetic studies in schizophrenia

Clinical classification systems may describe heterogeneous disorders implying that the current psychiatric classification might not be optimal for genetic studies. In contrast, endophenotypes describe quantifiable measures of neuropsychiatric functioning which might not be restricted to one clinical entity but are more easily attributable to genetic variations. Our ongoing project includes a broad range of schizophrenia-related endophenotypes. These comprise, among others, neuropsychological endophenotypes (working memory, attention/vigilance, verbal/visual learning and memory, speed of processing and problem solving). The aim was to analyse a broad range of neuropsychological endophenotypes in patients with schizophrenia, first degree relatives and healthy controls and to search for associated genes. Over 350 patients with schizophrenia according to DSM-IV, siblings and over 400 healthy volunteers were included. Facets of memory, learning and attention were assessed by the Wechsler Memory Scale-Revised. As expected, schizophrenic patients as well as their healthy siblings had clear deficits in these tasks comparing with healthy controls. Additionally, we will present data on the influence of common genetic variations (from the glutamatergic and dopaminergic system) on individual differences in these endophenotypes and discuss the findings in the context of schizophrenia.